Alignment and diagnostic device and methods for imaging and surgery at the irido-corneal angle of the eye

ABSTRACT

A device for visualizing an irido-corneal angle of an eye through a window of a patient interface configured to be placed on the eye includes and optics structure and at least one imaging apparatus. The optics structure is configured to engage with the patient interface to provide a line of sight through the window in the direction of the irido-corneal angle, and to subsequently disengage from the patient interface. The imaging apparatus is associated with the optics structure and aligned with the line of sight to enable capturing an image of the eye including the irido-corneal angle.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation application of U.S. patentapplication Ser. No. 16/844,655, filed Apr. 9, 2020, for “Alignment andDiagnostic Device and Methods for Imaging and Surgery at theIrido-Corneal Angle of the Eye,” the entire disclosure of which isincorporated herein by reference.

TECHNICAL FIELD

The present disclosure relates generally to the field of medical devicesand treatment of diseases in ophthalmology including glaucoma, and moreparticularly to an alignment and diagnostic device and methods forimaging and surgery at the irido-corneal angle of the eye.

BACKGROUND

Before describing the different types of glaucoma and current diagnosisand treatments options, a brief overview of the anatomy of the eye isprovided.

Anatomy of the Eye

With reference to FIGS. 1-3 , the outer tissue layer of the eye 1includes a sclera 2 that provides the structure of the eye's shape. Infront of the sclera 2 is a cornea 3 that is comprised of transparentlayers of tissue that allow light to enter the interior of the eye.Inside the eye 1 is a crystalline lens 4 that is connected to the eye byfiber zonules 5, which are connected to the ciliary body 6. Between thecrystalline lens 4 and the cornea 3 is an anterior chamber 7 thatcontains a flowing clear liquid called aqueous humor 8. Encircling theperimeter of the crystalline lens 4 is an iris 9 which forms a pupilaround the approximate center of the crystalline lens. A posteriorchamber 23 is an annular volume behind the iris 9 and bounded by theciliary body 6, fiber zonules 5, and the crystalline lens 4. Thevitreous humor 10 is located between the crystalline lens 4 and theretina 11. Light entering the eye is optically focused through thecornea 3 and crystalline lens.

With reference to FIG. 2 , the corneoscleral junction of the eye is theportion of the anterior chamber 7 at the intersection of the iris 9, thesclera 2, and the cornea 3. The anatomy of the eye 1 at thecorneoscleral junction includes a trabecular meshwork 12. The trabecularmeshwork 12 is a fibrous network of tissue that encircles the iris 9within the eye 1. In simplified, general terms the tissues of thecorneoscleral junction are arranged as follows: the iris 9 meets theciliary body 6, the ciliary body meets with the underside of the scleralspur 14, the top of the scleral spur serves as an attachment point forthe bottom of the trabecular meshwork 12. The ciliary body is presentmainly in the posterior chamber, but also extends into the very cornerof the anterior chamber 7. The network of tissue layers that make up thetrabecular meshwork 12 are porous and thus present a pathway for theegress of aqueous humor 8 flowing from the anterior chamber 7. Thispathway may be referred to herein as an aqueous humor outflow pathway,an aqueous outflow pathway, or simply an outflow pathway.

Referring to FIG. 3 , the pathway formed by the pores in the trabecularmeshwork 12 connect to a set of thin, porous tissue layers called theuveal 15, the corneoscleral meshwork 16, and the juxtacanalicular tissue17. The juxtacanalicular tissue 17, in turn, abuts a structure calledSchlemm's canal 18. The Schlemm's canal 18 carries a mixture of aqueoushumor 8 and blood from the surrounding tissue to drain into the venoussystem though a system of collector channels 19. As shown in FIG. 2 ,the vascular layer of the eye, referred to as the choroid 20, is next tothe sclera 2. A space, called the suprachoroidal space 21, may bepresent between the choroid 20 and the sclera 2. The general region nearthe periphery of the wedge between the cornea 3 and the iris 9, runningcircumferentially is called the irido-corneal angle 13. Theirido-corneal angle 13 may also be referred to as the corneal angle ofthe eye or simply the angle of the eye. The ocular tissues illustratedin FIG. 3 are all considered to be within the irido-corneal angle 13.

With reference to FIG. 4 , two possible outflow pathways for themovement of aqueous humor 8 include a trabecular outflow pathway 40 anda uveoscleral outflow pathway 42. Aqueous humor 8, which is produced bythe ciliary body 6, flows from the posterior chamber 23 through thepupil into the anterior chamber 7, and then exits the eye through one ormore of the two different outflow pathways 40, 42. Approximately 90% ofthe aqueous humor 8 leaves via the trabecular outflow pathway 40 bypassing through the trabecular meshwork 12, into the Schlemm's canal 18and through one or more plexus of collector channels 19 before drainingthrough a drain path 41 into the venous system. Any remaining aqueoushumor 8 leaves primarily through the uveoscleral outflow pathway 42. Theuveoscleral outflow pathway 42 passes through the ciliary body 6 faceand iris root into the suprachoroidal space 21 (shown in FIG. 2 ).Aqueous humor 8 drains from the suprachoroidal space 21, from which itcan be drained through the sclera 2.

The intra-ocular pressure of the eye depends on the aqueous humor 8outflow through the trabecular outflow pathway 40 and the resistance tooutflow of aqueous humor through the trabecular outflow pathway. Theintra-ocular pressure of the eye is largely independent of the aqueoushumor 8 outflow through the uveoscleral outflow pathway 42. Resistanceto the outflow of aqueous humor 8 through the trabecular outflow pathway40 may lead to elevated intra-ocular pressure of the eye, which is awidely recognized risk factor for glaucoma. Resistance through thetrabecular outflow pathway 40 may increase due a collapsed ormalfunctioning Schlemm's canal 18 and trabecular meshwork 12.

Referring to FIG. 5 , as an optical system, the eye 1 is represented byan optical model described by idealized centered and rotationallysymmetrical surfaces, entrance and exit pupils, and six cardinal points:object and image space focal points, first and second principal planes,and first and second nodal points. Angular directions relative to thehuman eye are often defined with respect to an optical axis 24, a visualaxis 26, a pupillary axis 28 and a line of sight 29 of the eye. Theoptical axis 24 is the symmetry axis, the line connecting the verticesof the idealized surfaces of the eye. The visual axis 26 connects thefoveal center 22 with the first and second nodal points to the object.The line of sight 29 connects the fovea through the exit and entrancepupils to the object. The pupillary axis 28 is normal to the anteriorsurface of the cornea 3 and directed to the center of the entrancepupil. These axes of the eye differ from one another only by a fewdegrees and fall within a range of what is generally referred to as thedirection of view.

Glaucoma

Glaucoma is a group of diseases that can harm the optic nerve and causevision loss or blindness. It is the leading cause of irreversibleblindness. Approximately 80 million people are estimated to haveglaucoma worldwide and of these, approximately 6.7 million arebilaterally blind. More than 2.7 million Americans over age 40 haveglaucoma. Symptoms start with loss of peripheral vision and can progressto blindness.

There are two forms of glaucoma, one is referred to as closed-angleglaucoma, the other as open-angled glaucoma. With reference to FIGS. 1-4, in closed-angle glaucoma, the iris 9 in a collapsed anterior chamber 7may obstruct and close off the flow of aqueous humor 8. In open-angleglaucoma, which is the more common form of glaucoma, the permeability ofocular tissue may be affected by irregularities in the juxtacanaliculartissue 17 and inner wall of Schlemm's canal 18 a, blockage of tissue inthe irido-corneal angle 13 along the trabecular outflow pathway 40.

As previously stated, elevated intra-ocular pressure (TOP) of the eye,which damages the optic nerve, is a widely recognized risk factor forglaucoma. However, not every person with increased eye pressure willdevelop glaucoma, and glaucoma can develop without increased eyepressure. Nonetheless, it is desirable to reduce elevated TOP of the eyeto reduce the risk of glaucoma.

Methods of diagnosing conditions of the eye of a patient with glaucomainclude visual acuity tests and visual field tests, dilated eye exams,tonometry, i.e., measuring the intra-ocular pressure of the eye, andpachymetry, i.e., measuring the thickness of the cornea. Deteriorationof vision starts with the narrowing of the visual field and progressesto total blindness. Imaging methods include slit lamp examination,observation of the irido-corneal angle with a gonioscopic lens andoptical coherence tomography (OCT) imaging of the anterior chamber andthe retina

Once diagnosed, some clinically proven treatments are available tocontrol or lower the intra-ocular pressure of the eye to slow or stopthe progress of glaucoma. The most common treatments include: 1)medications, such as eye drops or pills, 2) laser surgery, and 3)traditional surgery. Treatment usually begins with medication. However,the efficacy of medication is often hindered by patient non-compliance.When medication does not work for a patient, laser surgery is typicallythe next treatment to be tried. Traditional surgery is invasive, morehigh risk than medication and laser surgery, and has a limited timewindow of effectiveness. Traditional surgery is thus usually reserved asa last option for patients whose eye pressure cannot be controlled withmedication or laser surgery.

Laser Surgery

With reference to FIG. 2 , laser surgery for glaucoma targets thetrabecular meshwork 12 to decrease aqueous humor 8 flow resistance.Common laser treatments include Argon Laser Trabeculoplasty (ALT),Selective Laser Trabeculoplasty (SLT) and Excimer Laser Trabeculostomy(ELT).

ALT was the first laser trabeculoplasty procedure. During the procedure,an argon laser of 514 nm wavelength is applied to the trabecularmeshwork 12 around 180 degrees of the circumference of the irido-cornealangle 13. The argon laser induces a thermal interaction with the oculartissue that produces openings in the trabecular meshwork 12. ALT,however, causes scarring of the ocular tissue, followed by inflammatoryresponses and tissue healing that may ultimately close the openingthrough the trabecular meshwork 12 formed by the ALT treatment, thusreducing the efficacy of the treatment. Furthermore, because of thisscarring, ALT therapy is typically not repeatable.

SLT is designed to lower the scarring effect by selectively targetingpigments in the trabecular meshwork 12 and reducing the amount of heatdelivered to surrounding ocular tissue. During the procedure, asolid-state laser of 532 nm wavelength is applied to the trabecularmeshwork 12 between 180 to 360 degrees around the circumference of theirido-corneal angle 13 to remove the pigmented cells lining thetrabeculae which comprise the trabecular meshwork. The collagenultrastructure of the trabecular meshwork is preserved during SLT. SLTtreatment can be repeated, but subsequent treatments have lower effectson TOP reduction.

ELT uses a 308 nm wavelength ultraviolet (UV) excimer laser andnon-thermal interaction with ocular tissue to treat the trabecularmeshwork 12 and inner wall of Schlemm's canal in a manner that does notinvoke a healing response. Therefore, the TOP lowering effect lastslonger. However, because the UV light of the laser cannot penetrate deepinto the eye, the laser light is delivered to the trabecular meshwork 12via an optical fiber inserted into the eye 1 through an opening and thefiber is brought into contact with the trabecular meshwork. Theprocedure is highly invasive and is generally practiced simultaneouslywith cataract procedures when the eye is already surgically open. LikeALT and SLT, ELT also lacks control over the amount of TOP reduction.

In these laser treatments, and other ophthalmic surgeries involving alaser, it is necessary to stabilize and fix the position of the eyerelative to an optical delivery system through which the laser isoutput. This is particularly needed wherever highly precise incisionsare created in the eye. In these treatments, a patient interface isfirst docked onto the eye. Suction is applied to a suction ring aroundthe patient interface to fix the patient interface onto the eye. Theoptical delivery system is then locked into the patient interface. Inthis manner, the patient's eye and the laser output from the opticaldelivery system is aligned.

For glaucoma surgery the task of accurately positioning the patientinterface is complicated by the fact that the laser treatment involvesocular tissue in the irido-corneal angle of the eye. Ophthalmic surgicalinstruments that access the irido-corneal angle of the eye have alimited surgical range in three-dimensional space where thespecifications of the laser, imaging capability of the instrument andfocusability of the laser are satisfied. Thus, proper alignment betweenthe eye and optical delivery system is critical. Without such alignment,the intended surgical location on the eye may fall outside the field ofview or the surgical range of the optical delivery system. In that caseundesired repeated undocking and realignment of the eye is necessary.

SUMMARY

The present disclosure relates to a device for visualizing anirido-corneal angle of an eye through a window of a patient interfaceconfigured to be placed on the eye. The device includes an opticsstructure and at least one imaging apparatus. The optics structure isconfigured to engage with the patient interface to provide a line ofsight through the window in a direction of the irido-corneal angle, andto subsequently disengage from the patient interface. The at least oneimaging apparatus is associated with the optics structure and alignedwith the line of sight to enable capturing an image of the eye includingthe irido-corneal angle.

The optics structure may be configured to provide the line of sight inthe direction of the irido-corneal angle around at least a portion of acircumferential extent of the irido-corneal angle. The optics structuremay be configured to provide the line of sight in the direction of theirido-corneal angle around an entire circumferential extent of theirido-corneal angle. The optics structure may be configured to rotaterelative to the patient interface to enable a capturing of images atvarious angular positions around a circumferential extent of theirido-corneal angle.

The at least one imaging apparatus is configured to couple to the opticsstructure and the optics structure is configured to rotate relative tothe patient interface together with the at least one imaging apparatus.The device may further include a locking mechanism associated with theoptics structure. The locking mechanism is configured to enable fixationof the optics structure relative to the patient interface at variousangular positions around a circumferential extent of the irido-cornealangle.

The imaging apparatus may be a camera. The imaging apparatus may includeone or more optical coherence tomography (OCT) components configured tocouple with an OCT apparatus remote from the device. The imagingapparatus may include a dual aiming beam apparatus configured totransmit a first beam of light and a second beam light in the directionof the line of sight into the irido-corneal angle. The imaging apparatusmay include a first fiber optic cable having an output aligned in thedirection of the line of sight and a second fiber optic cable having anoutput aligned in the direction of the line of sight, wherein the firstand second fiber optic cables are configured to couple to a dual aimingbeam apparatus remote from the device so that the first fiber opticcable receives a first beam of light and the second fiber optic cablereceives a second beam light. The imaging apparatus may be a secondharmonic light detector aligned with the line of sight and configured todetermine a location of a focus of a laser beam based on changes in anintensity of a spot of second harmonic light generated by an encounterbetween the focus and tissue. The device may further include aninterface configured to couple to a laser source and to transmit a laserbeam output by the laser source in the direction of the line of sight.

The present disclosure also relates to a method of aligning an eye forlaser treatment of a target volume of ocular tissue in an irido-cornealangle by a laser surgical instrument having a surgical range. The methodincludes presenting an image of the eye on a display, wherein: the imageis captured by an alignment and diagnostic device that is engaged with apatient interface to provide a line of sight in a direction of theirido-corneal angle, the display includes a surgical area overlaycorresponding to the surgical range of the laser surgical instrument,and the alignment and diagnostic device is independent of the lasersurgical instrument and is configured to engage with and subsequentlydisengage from the patient interface. The method also includes updatingthe display of the image during a movement of the patient interface andthe alignment and diagnostic device relative to the eye, andimmobilizing the patient interface relative to the eye when the displayindicates that the target volume of ocular tissue is within the surgicalarea overlay.

The surgical area overlay may include a coarse surgical area overlay anda fine surgical area overlay located within the coarse surgical areaoverlay. The surgical area overlay may further include a circumferencescanning mark, which indicates a length and an orientation of acircumferential optical coherence tomography (OCT) scan of an OCTimaging apparatus associated with the laser surgical instrument. Thesurgical area overlay may further include a transverse scanning markthat indicates a length and an orientation of a transverse opticalcoherence tomography (OCT) scan of an OCT imaging apparatus associatedwith the laser surgical instrument.

The method may further include, subsequent to immobilizing the patientinterface relative to the eye, recording a circumferential angularposition of the target volume of ocular tissue from a rotationalregistration of the alignment and diagnostic device; and removing thealignment and diagnostic device from the patient interface. The methodmay further include, subsequent to removing the alignment and diagnosticdevice from the patient interface: coupling the laser surgicalinstrument to the patient interface; setting a circumferential angularposition of the laser surgical instrument to the circumferential angularposition recorded for the alignment and diagnostic device; and focusinglight from a laser at a spot in the target volume of ocular tissue; andapplying optical energy at the spot in the target volume of oculartissue. The method may further include, prior to focusing light from thelaser at a spot in the target volume of ocular tissue: presenting animage of the eye on a display, wherein, the image is captured by avisual microscope optically coupled to the patient interface, and thedisplay includes a surgical area overlay corresponding to the surgicalrange of the laser surgical instrument.

The method may further include prior to immobilizing the patientinterface relative to the eye, determining if a depth fiducial of thetarget volume of ocular tissue is within a depth range of the lasersurgical instrument. The determining may be based on a relative locationof spots of light output by a dual aiming beam apparatus and a surfaceof the target volume of ocular tissue. The determining may be based onan interaction of second harmonic light and one or more anatomicallandmarks of the target volume of ocular tissue.

It is understood that other aspects of apparatuses and methods willbecome apparent to those skilled in the art from the following detaileddescription, wherein various aspects of apparatuses and methods areshown and described by way of illustration. As will be realized, theseaspects may be implemented in other and different forms and its severaldetails are capable of modification in various other respects.Accordingly, the drawings and detailed description are to be regarded asillustrative in nature and not as restrictive.

BRIEF DESCRIPTION OF THE DRAWINGS

The patent or application file contains at least one drawing executed incolor. Copies of this patent or patent application publication withcolor drawings(s) will be provided by the Office upon request andpayment of the necessary fee.

Various aspects of systems, apparatuses, and methods will now bepresented in the detailed description by way of example, and not by wayof limitation, with reference to the accompanying drawings, wherein:

FIG. 1 is a sectional schematic illustration of a human eye and itsinterior anatomical structures.

FIG. 2 is a sectional schematic illustration of the irido-corneal angleof the eye of FIG. 1 .

FIG. 3 is a sectional schematic illustration detailing anatomicalstructures in the irido-corneal angle of FIG. 2 , including thetrabecular meshwork, Schlemm's canal, and one or more collector channelsbranching from the Schlemm's canal.

FIG. 4 is a sectional schematic illustration of various outflow pathwaysfor aqueous humor through the trabecular meshwork, Schlemm's canal, andcollector channels of FIG. 3 .

FIG. 5 is a sectional schematic illustration of a human eye showingvarious axes associated with the eye.

FIG. 6 is a sectional schematic illustration of an angled beam pathalong which one or more light beams may access the irido-corneal angleof the eye.

FIG. 7 is a block diagram of an integrated surgical system fornon-invasive glaucoma surgery including a control system, a femtosecondlaser source, an OCT imaging apparatus, a visual observation apparatus,a dual aiming beam apparatus, a second harmonic light detectionapparatus, beam conditioners and scanners, beam combiners, a focusingobjective, and a patient interface.

FIG. 8 is a detailed block diagram of the integrated surgical system ofFIG. 7 .

FIGS. 9A and 9B are schematic illustrations of the focusing objective ofthe integrated surgical system of FIG. 7 coupled to (FIG. 9A) anddecoupled from (FIG. 9B) the patient interface of the integratedsurgical system of FIG. 7 .

FIG. 9C is a schematic illustration of components of the focusingobjective and the patient interface included in FIGS. 9A and 9B.

FIG. 10 is a three-dimensional schematic illustration of anatomicalstructures in the irido-corneal angle, including the trabecularmeshwork, Schlemm's canal, a collector channel branching from theSchlemm's canal, and a surgical volume of ocular tissue to be treated bythe integrated surgical system of FIG. 7 .

FIG. 11 is a two-dimensional schematic illustration of anatomicalstructures in the irido-corneal angle and a laser treatment pattern tobe applied by the integrated surgical system of FIG. 7 to affect asurgical volume of ocular tissue between the Schlemm's canal and theanterior chamber as shown in FIG. 10 .

FIG. 12 is a three-dimensional schematic illustration of FIG. 10subsequent to treatment of the surgical volume of ocular tissue by alaser based on the laser treatment pattern of FIG. 11 that forms anopening between the Schlemm's canal and the anterior chamber.

FIG. 13 is a block diagram of an alignment and diagnostic device forvisualizing an irido-corneal angle of an eye including an imagingapparatus and an optics structure that couples to a patient interface.

FIGS. 14A and 14B are schematic illustrations of an alignment anddiagnostic device for visualizing an irido-corneal angle of an eye.

FIG. 15A is an image of a portion of an irido-corneal angle of an eyecaptured by an alignment and diagnostic device having a single facetmirror.

FIG. 15B is image of portions of an irido-corneal angle captured by analignment and diagnostic device having four facet mirrors.

FIG. 16 is an image of a portion of an irido-corneal angle of an eyecaptured by a camera of an alignment and diagnostic device.

FIGS. 17A and 17B images of a portion of an irido-corneal angle of aneye captured by an OCT apparatus in conjunction with an OCT component ofan alignment and diagnostic device.

FIGS. 18A, 18B and 18C are illustrations of an alignment and diagnosticdevice together with a patient interface.

FIG. 19A is the image of FIG. 16 as it would appear on a display of analignment and diagnostic device, with a surgical area overlay to assistin aligning the device relative to a target surgical location of theirido-corneal angle.

FIGS. 19B and 19C are schematic representations of an image of anirido-corneal angle of an eye captured by a camera of an alignment anddiagnostic device with a surgical area overlay.

FIGS. 20A and 20B are illustrations of a patient positioned on asurgical bed in proximity with an attachment arm of an integratedsurgical system.

FIGS. 21A and 21B are a flowchart of a method of laser surgicaltreatment of an eye that employs the alignment and diagnostic device ofFIG. 13 .

FIGS. 22A and 22B are schematic illustrations of the alignment anddiagnostic device together and patient interface being slid and tilted(FIG. 22A) and rotated (FIG. 22B) relative to the eye.

DETAILED DESCRIPTION

Disclosed herein is an alignment and diagnostic device and methods forimaging and surgery at the irido-corneal angle of the eye. The alignmentand diagnostic device is a portable, handheld device that removablycouples with a patient interface placed on the eye. The device enablesvisualization of the irido-corneal angle of the eye. Such visualizationmay be provided, for example, by a camera included in the device, or anoptical coherence tomography (OCT) imaging component included in thedevice that couples to an OCT imaging apparatus. Movement of the deviceand patient interface relative to the eye during visualization enable analignment of the patient interface on the eye that places a targetsurgical location in the irido-corneal angle in the surgical range of anintegrated surgical system. Upon placement of the target surgicallocation in the surgical range, the patient interface is secured to theeye, the alignment and diagnostic device is removed from the eye, andthe integrated surgical system is coupled to the patient interface fordelivery of laser treatment to the target surgical location.

The integrated surgical system coupled to the patient interface isconfigured to reduce intraocular pressure in an eye having a cornea, ananterior chamber, and an irido-corneal angle comprising an aqueous humoroutflow pathway formed of a trabecular meshwork, a Schlemm's canal, andone or more collector channels branching from the Schlemm's canal. Theintegrated surgical system also includes a first optical subsystem and asecond optical subsystem. The first optical subsystem includes a windowconfigured to be coupled to the cornea and an exit lens configured to becoupled to the window. The second optical subsystem includes an opticalcoherence tomography (OCT) imaging apparatus configured to output an OCTbeam, a laser source configured to output a laser beam, and a pluralityof components, e.g., lenses and mirrors, configured to condition,combine, or direct the OCT beam and the laser beam toward the firstoptical subsystem.

The integrated surgical system also includes a control system coupled tothe OCT imaging apparatus, the laser source, and the second opticalsubsystem. The controller is configured to instruct the OCT imagingapparatus to output an OCT beam and the laser source to output a laserbeam, for delivery through the cornea, and the anterior chamber into theirido-corneal angle. In one configuration, the control system controlsthe second optical subsystem, so the OCT beam and the laser beam aredirected into the first optical subsystem along a second optical axisthat is offset from the first optical axis and that extends into theirido-corneal angle along an angled beam path 30.

Directing each of an OCT beam and a laser beam along the same secondoptical axis into the irido-corneal angle of the eye is beneficial inthat it enables direct application of the result of the evaluation ofthe condition into the treatment plan and surgery with precision in oneclinical setting. Furthermore, combining OCT imaging and laser treatmentallows targeting the ocular tissue with precision not available with anyexisting surgical systems and methods. Surgical precision afforded bythe integrated surgical system allows for the affecting of only thetargeted tissue of microscopic size and leaves the surrounding tissueintact. The microscopic size scale of the affected ocular tissue to betreated in the irido-corneal angle of the eye ranges from a fewmicrometers to a few hundred micrometers. For example, with reference toFIGS. 2 and 3 , the cross-sectional size of the normal Schlemm's canal18 is an oval shape of a few tens of micrometers by a few hundredmicrometers. The diameter of collector channels 19 and veins is a fewtens of micrometers. The thickness of the juxtacanalicular tissue 17 isa few micrometers, the thickness of the trabecular meshwork 12 is arounda hundred micrometers.

The control system of the integrated surgical system is furtherconfigured to instruct the laser source to modify a volume of oculartissue within the outflow pathway to reduce a pathway resistance presentin one or more of the trabecular meshwork, the Schlemm's canal, and theone or more collector channels by applying the laser beam to oculartissue defining the volume to thereby cause photo-disruptive interactionwith the ocular tissue to reduce the pathway resistance or create a newoutflow pathway.

The laser source may be a femtosecond laser. Femtosecond lasers providenon-thermal photo-disruption interaction with ocular tissue to avoidthermal damage to surrounding tissue. Further, unlike other surgicalmethods, with femtosecond laser treatment opening surface incisionspenetrating the eye can be avoided, enabling a non-invasive treatment.Instead of performing the treatment in a sterile surgical room, thenon-invasive treatment can be performed in a non-sterile outpatientfacility.

An additional imaging component may be included the integrated surgicalsystem to provide direct visual observation of the irido-corneal anglealong an angle of visual observation. For example, a microscope orimaging camera may be included to assist the surgeon in the process ofdocking the eye to the patient interface or an immobilizing device,location of ocular tissues in the eye and observing the progress of thesurgery. The angle of visual observation can also be along the angledbeam path 30 to the irido-corneal angle 13 through the cornea 3 and theanterior chamber 7.

Images from the OCT imaging apparatus and the additional imagingcomponent providing visual observation, e.g. microscope, are combined ona display device such as a computer monitor. Different images can beregistered and overlaid on a single window, enhanced, processed,differentiated by false color for easier understanding. Certain featuresare computationally recognized by a computer processor, imagerecognition and segmentation algorithm can be enhanced, highlighted,marked for display. The geometry of the treatment plan can also becombined and registered with imaging information on the display deviceand marked up with geometrical, numerical and textual information. Thesame display can also be used for user input of numerical, textual andgeometrical nature for selecting, highlighting and marking features,inputting location information for surgical targeting by keyboard,mouse, cursor, touchscreen, audio or other user interface devices.

OCT Imaging

The main imaging component of the integrated surgical system disclosedherein is an OCT imaging apparatus. OCT technology may be used todiagnose, locate and guide laser surgery directed to the irido-cornealangle of the eye. For example, with reference to FIGS. 1-3 , OCT imagingmay be used to determine the structural and geometrical conditions ofthe anterior chamber 7, to assess possible obstruction of the trabecularoutflow pathway 40 and to determine the accessibility of the oculartissue for treatment. As previously described, the iris 9 in a collapsedanterior chamber 7 may obstruct and close off the flow of aqueous humor8, resulting in closed-angle glaucoma. In open-angle glaucoma, where themacroscopic geometry of the angle is normal, the permeability of oculartissue may be affected, by blockage of tissue along the trabecularoutflow pathway 40 or by the collapse of the Schlemm's canal 18 orcollector channels 19.

OCT imaging can provide the necessary spatial resolution, tissuepenetration and contrast to resolve microscopic details of oculartissue. When scanned, OCT imaging can provide two-dimensional (2D)cross-sectional images of the ocular tissue. As another aspect of theintegrated surgical system, 2D cross-sectional images may be processedand analyzed to determine the size, shape and location of structures inthe eye for surgical targeting. It is also possible to reconstructthree-dimensional (3D) images from a multitude of 2D cross-sectionalimages but often it is not necessary. Acquiring, analyzing anddisplaying 2D images is faster and can still provide all informationnecessary for precise surgical targeting.

OCT is an imaging modality capable of providing high resolution imagesof materials and tissue. Imaging is based on reconstructing spatialinformation of the sample from spectral information of scattered lightfrom within the sample. Spectral information is extracted by using aninterferometric method to compare the spectrum of light entering thesample with the spectrum of light scattered from the sample. Spectralinformation along the direction that light is propagating within thesample is then converted to spatial information along the same axis viathe Fourier transform. Information lateral to the OCT beam propagationis usually collected by scanning the beam laterally and repeated axialprobing during the scan. 2D and 3D images of the samples can be acquiredthis way. Image acquisition is faster when the interferometer is notmechanically scanned in a time domain OCT, but interference from a broadspectrum of light is recorded simultaneously, this implementation iscalled a spectral domain OCT. Faster image acquisition may also beobtained by scanning the wavelength of light rapidly from a wavelengthscanning laser in an arrangement called a swept-source OCT.

The axial spatial resolution limit of the OCT is inversely proportionalto the bandwidth of the probing light used. Both spectral domain andswept source OCTs are capable of axial spatial resolution below 5micrometers (μm) with sufficiently broad bandwidth of 100 nanometers(nm) or more. In the spectral domain OCT, the spectral interferencepattern is recorded simultaneously on a multichannel detector, such as acharge coupled device (CCD) or complementary metal oxide semiconductor(CMOS) camera, while in the swept source OCT the interference pattern isrecorded in sequential time steps with a fast optical detector andelectronic digitizer. There is some acquisition speed advantage of theswept source OCT but both types of systems are evolving and improvingrapidly, and resolution and speed is sufficient for purposes of theintegrated surgical system disclosed herein. Stand-alone OCT systems andOEM components are now commercially available from multiple vendors,such as Optovue Inc., Fremont, Calif., Topcon Medical Systems, Oakland,N.J., Carl Zeiss Meditec AG, Germany, Nidek, Aichi, Japan, Thorlabs,Newton, N.J., Santec, Aichi, Japan, Axsun, Billercia, Mass., and othervendors.

Femtosecond Laser Source

The preferred surgical component of the integrated surgical systemdisclosed herein is a femtosecond laser. A femtosecond laser provideshighly localized, non-thermal photo-disruptive laser-tissue interactionwith minimal collateral damage to surrounding ocular tissue.Photo-disruptive interaction of the laser is utilized in opticallytransparent tissue. The principal mechanism of laser energy depositioninto the ocular tissue is not by absorption but by a highly nonlinearmultiphoton process. This process is effective only at the focus of thepulsed laser where the peak intensity is high. Regions where the beam istraversed but not at the focus are not affected by the laser. Therefore,the interaction region with the ocular tissue is highly localized bothtransversally and axially along the laser beam. The process can also beused in weakly absorbing or weakly scattering tissue. While femtosecondlasers with photo-disruptive interactions have been successfully used inophthalmic surgical systems and commercialized in other ophthalmic laserprocedures, none have been used in an integrated surgical system thataccesses the irido-corneal angle.

In known refractive procedures, femtosecond lasers are used to createcorneal flaps, pockets, tunnels, arcuate incisions, lenticule shapedincisions, partial or fully penetrating corneal incisions forkeratoplasty. For cataract procedures the laser creates a circular cuton the capsular bag of the eye for capsulotomy and incisions of variouspatterns in the lens for braking up the interior of the crystalline lensto smaller fragments to facilitate extraction. Entry incisions throughthe cornea opens the eye for access with manual surgical devices and forinsertions of phacoemulsification devices and intra-ocular lensinsertion devices. Several companies have commercialized such surgicalsystems, among them the IntraLase system now available from Johnson &Johnson Vision, Santa Ana, Calif., The LenSx and WaveLight systems fromAlcon, Fort Worth, Tex., other surgical systems from Bausch and Lomb,Rochester, N.Y., Carl Zeiss Meditec AG, Germany, Ziemer, Port,Switzerland, and LENSAR, Orlando, Fla.

These existing systems are developed for their specific applications,for surgery in the cornea, and the crystalline lens and its capsular bagand are not capable of performing surgery in the irido-corneal angle 13for several reasons. First, the irido-corneal angle 13 is not accessiblewith these surgical laser systems because the irido-corneal angle is toofar out in the periphery and is outside of surgical range of thesesystems. Second, the angle of the laser beam from these systems, whichis along the optical axis 24 to the eye 1, is not appropriate toreaching the irido-corneal angle 13, where there is significantscattering and optical distortion at the applied wavelength. Third, anyimaging capabilities these systems may have do not have theaccessibility, penetration depth and resolution to image the tissuealong the trabecular outflow pathway 40 with sufficient detail andcontrast.

In accordance with the integrated surgical system disclosed herein,clear access to the irido-corneal angle 13 is provided along the angledbeam path 30. The tissue, e.g., cornea 3 and the aqueous humor 8 in theanterior chamber 7, along this angled beam path 30 is transparent forwavelengths from approximately 400 nm to 2500 nm and femtosecond lasersoperating in this region can be used. Such mode locked lasers work attheir fundamental wavelength with Titanium, Neodymium or Ytterbiumactive material. Non-linear frequency conversion techniques known in theart, frequency doubling, tripling, sum and difference frequency mixingtechniques, optical parametric conversion can convert the fundamentalwavelength of these lasers to practically any wavelength in theabove-mentioned transparent wavelength range of the cornea.

Existing ophthalmic surgical systems apply lasers with pulse durationslonger than 1 ns have higher photo-disruption threshold energy, requirehigher pulse energy and the dimension of the photo-disruptiveinteraction region is larger, resulting in loss of precision of thesurgical treatment. When treating the irido-corneal angle 13, however,higher surgical precision is required. To this end, the integratedsurgical system may be configured to apply lasers with pulse durationsfrom 10 femtosecond (fs) to 1 nanosecond (ns) for generatingphoto-disruptive interaction of the laser beam with ocular tissue in theirido-corneal angle 13. While lasers with pulse durations shorter than10 fs are available, such laser sources are more complex and moreexpensive. Lasers with the described desirable characteristics, e.g.,pulse durations from 10 femtosecond (fs) to 1 nanosecond (ns), arecommercially available from multiple vendors, such as Newport, Irvine,Calif., Coherent, Santa Clara, Calif., Amplitude Systems, Pessac,France, NKT Photonics, Birkerod, Denmark, and other vendors.

Accessing the Irido-Corneal Angle

An important feature afforded by the integrated surgical system isaccess to the targeted ocular tissue in the irido-corneal angle 13. Withreference to FIG. 6 , the irido-corneal angle 13 of the eye may beaccessed via the integrated surgical system along an angled beam path 30passing through the cornea 3 and through the aqueous humor 8 in theanterior chamber 7. For example, one or more of an imaging beam, e.g.,an OCT beam and/or a visual observation beam, and a laser beam mayaccess the irido-corneal angle 13 of the eye along the angled beam path30.

An optical system disclosed herein is configured to direct a light beamto an irido-corneal angle 13 of an eye along an angled beam path 30. Theoptical system includes a first optical subsystem and a second opticalsubsystem. The first optical subsystem includes a window formed of amaterial with a refractive index n_(w) and has opposed concave andconvex surfaces. The first optical subsystem also includes an exit lensformed of a material having a refractive index n_(x). The exit lens alsohas opposed concave and convex surfaces. The concave surface of the exitlens is configured to couple to the convex surface of the window todefine a first optical axis extending through the window and the exitlens. The concave surface of the window is configured to detachablycouple to a cornea of the eye with a refractive index n_(c) such that,when coupled to the eye, the first optical axis is generally alignedwith the direction of view of the eye.

The second optical subsystem is configured to output a light beam, e.g.,an OCT beam or a laser beam. The optical system is configured so thatthe light beam is directed to be incident at the convex surface of theexit lens along a second optical axis at an angle α that is offset fromthe first optical axis. The respective geometries and respectiverefractive indices n_(x), and n_(w) of the exit lens and window areconfigured to compensate for refraction and distortion of the light beamby bending the light beam so that it is directed through the cornea 3 ofthe eye toward the irido-corneal angle 13. More specifically, the firstoptical system bends the light beam to that the light beam exits thefirst optical subsystem and enters the cornea 3 at an appropriate angleso that the light beam progresses through the cornea and the aqueoushumor 8 in a direction along the angled beam path 30 toward theirido-corneal angle 13.

Accessing the irido-corneal angle 13 along the angled beam path 30provides several advantages. An advantage of this angled beam path 30 tothe irido-corneal angle 13 is that the OCT beam and laser beam passesthrough mostly clear tissue, e.g., the cornea 3 and the aqueous humor 8in the anterior chamber 7. Thus, scattering of these beams by tissue isnot significant. With respect to OCT imaging, this enables the use ofshorter wavelength, less than approximately 1 micrometer, for the OCT toachieve higher spatial resolution. An additional advantage of the angledbeam path 30 to the irido-corneal angle 13 through the cornea 3 and theanterior chamber 7 is the avoidance of direct laser beam or OCT beamlight illuminating the retina 11. As a result, higher average powerlaser light and OCT light can be used for imaging and surgery, resultingin faster procedures and less tissue movement during the procedure.

Another important feature provided by the integrated surgical system isaccess to the targeted ocular tissue in the irido-corneal angle 13 in away that reduces beam discontinuity. To this end, the window and exitlens components of the first optical subsystem are configured to reducethe discontinuity of the optical refractive index between the cornea 3and the neighboring material and facilitate entering light through thecornea at a steep angle.

Having thus generally described the integrated surgical system and someof its features and advantages, a more detailed description of thesystem and its component parts follows.

Integrated Surgical System

With reference to FIG. 7 , an integrated surgical system 1000 fornon-invasive glaucoma surgery includes a control system 100, a surgicalcomponent 200, a first imaging apparatus 300, a second imaging apparatus400, a dual aiming beam apparatus 450, and a second harmonic lightdetection apparatus 460. In the embodiment of FIG. 7 , the surgicalcomponent 200 is a femtosecond laser source, the first imaging apparatus300 is an OCT imaging apparatus, and the optional second imagingapparatus 400 is a visual observation apparatus, comprising a videocamera and an illumination source for viewing or capturing images of asurgical field. The dual aiming beam apparatus 450 outputs a pair ofbeams of light, referred to herein as aiming beams, for use in detectinga surface of ocular tissue in the surgical field. The second harmoniclight detection apparatus 460 may be, for example, a photodetectorconfigured to detect second harmonic light generated in the surgicalfield or a video camera instrumented with a visible filter centered nearor at 515 nm (with a bandpass of 20-50 nm) that detects green lightgenerated by surface second harmonic generation. Other components of theintegrated surgical system 1000 include beam conditioners and scanners500, beam combiners 600, a focusing objective 700, and a patientinterface 800.

The control system 100 may be a single computer or and plurality ofinterconnected computers configured to control the hardware and softwarecomponents of the other components of the integrated surgical system1000. A user interface 110 of the control system 100 acceptsinstructions from a user and displays information for observation by theuser. Input information and commands from the user include but are notlimited to system commands, motion controls for docking the patient'seye to the system, selection of pre-programmed or live generatedsurgical plans, navigating through menu choices, setting of surgicalparameters, responses to system messages, determining and acceptance ofsurgical plans and commands to execute the surgical plan. Outputs fromthe system towards the user includes but are not limited to display ofsystem parameters and messages, display of images of the eye, graphical,numerical and textual display of the surgical plan and the progress ofthe surgery.

The control system 100 is connected to the other components 200, 300,400, 450, 460, 500 of the integrated surgical system 1000. Signalsbetween the control system 100 and the femtosecond laser source 200function to control internal and external operation parameters of thelaser source, including for example, power, repetition rate and beamshutter. Control and feedback signals between the control system 100 andthe OCT imaging apparatus 300 function to control OCT beam scanningparameters, and the acquiring, analyzing and displaying of OCT images.Control signals between the control system 100 and the dual aiming beamapparatus 450 function to control the output of beams of light by theone or more aiming beam sources of the dual aiming beam apparatus.Control signals between the control system 100 and the visualobservation apparatus 400 function to control the capturing, imageprocessing and displaying of spots of light on tissue surfaces in thesurgical field that result from the one or more beams of light output bythe dual aiming beam apparatus 450. To this end, the line of sight ofthe visual observation apparatus 400 is aligned with the femtosecondlaser and directed into the irido-corneal angle of the eye. Signalsbetween the control system 100 and the second harmonic light detectionapparatus 460 function to control the operation of the second harmoniclight detection apparatus, and the detecting of second harmonic lightgenerated by an encounter between the focus of the laser and tissue inthe irido-corneal angle of the eye. To this end, the line of sight ofthe second harmonic light detection apparatus 460 is aligned with thefemtosecond laser and directed into the irido-corneal angle of the eye.Control signals from the control system 100 to the beam conditioner andscanners 500 function to control the focus of the laser beam output bythe femtosecond laser source 200. Such control may include advancing thefocus of the laser beam in the direction of propagation of the laser orin the direction opposite the direction of propagation of the laser, andscanning the focus.

Laser beams 201 from the femtosecond laser source 200 and OCT beams 301from the OCT imaging apparatus 300 are directed towards a unit of beamconditioners and scanners 500. Different kind of scanners can be usedfor the purpose of scanning the laser beam 201 and the OCT beam 301. Forscanning transversal to a beam 201, 301, angular scanning galvanometerscanners are available for example from Cambridge Technology, Bedford,Mass., Scanlab, Munich, Germany. To optimize scanning speed, the scannermirrors are typically sized to the smallest size, which still supportthe required scanning angles and numerical apertures of the beams at thetarget locations. The ideal beam size at the scanners is typicallydifferent from the beam size of the laser beam 201 or the OCT beam 301,and different from what is needed at the entrance of a focusingobjective 700. Therefore, beam conditioners are applied before, after orin between individual scanners. The beam conditioner and scanners 500includes scanners for scanning the beam transversally and axially. Axialscanning changes the depth of the focus at the target region. Axialscanning can be performed by moving a lens axially in the beam path witha servo or stepper motor.

The laser beam 201 and the OCT beam 301 are combined with dichroic,polarization or other kind of beam combiners 600 to reach a commontarget volume or surgical volume in the eye. Likewise, an illuminationbeam 401 from the visual observation apparatus 400 and a pair of aimingbeams of light 451 a, 451 b from the dual aiming beam apparatus 450 arecombined by dichroic, polarization or other kind of beam combiners 600to reach the common target volume or surgical volume in the eye. In anintegrated surgical system 1000 having a femtosecond laser source 200,an OCT imaging apparatus 300, a visual observation apparatus 400, and andual aiming beam apparatus 450, the individual beams 201, 301, 401, 451a, 451 b for each of these components may be individually optimized andmay be collinear or non-collinear to one another. The beam combiner 600uses dichroic or polarization beam splitters to split and recombinelight with different wavelength and/or polarization. The beam combiner600 may also include optics to change certain parameters of theindividual beams 201, 301, 401, 451 a, 451 b such as beam size, beamangle and divergence. Integrated visual illumination, observation orimaging devices assist the surgeon in docking the eye to the system andidentifying surgical locations.

To facilitate locating a focus of a femtosecond laser beam 201 at ornear a target structure of ocular tissue, the second harmonic lightdetection apparatus 460 of the integrated surgical system 1000 generatesinformation indicative of the presence or absence of second harmoniclight in the irido-corneal angle of the eye. To this end, in oneembodiment, the second harmonic light detection apparatus 460 isconfigured to detect for a second harmonic light beam 451 using aphotodetector, and to provide an intensity profile of second harmonicgenerated light as a function of scan depth of the second harmonicsignal as the focus of the femtosecond laser beam 201 is advanced.Details on the second harmonic light detection apparatus 460 areprovided in U.S. patent application Ser. No. 16/723,883, titled “Systemand Method for Locating a Structure of Ocular Tissue for GlaucomaSurgery Based on Second Harmonic Light,” which is hereby incorporated byreference.

To resolve ocular tissue structures of the eye in sufficient detail, theOCT imaging apparatus 300 of the integrated surgical system 1000 mayprovide an OCT beam having a spatial resolution of several micrometers.The resolution of the OCT beam is the spatial dimension of the smallestfeature that can be recognized in the OCT image. It is determined mostlyby the wavelength and the spectral bandwidth of the OCT source, thequality of the optics delivering the OCT beam to the target location inthe eye, the numerical aperture of the OCT beam and the spatialresolution of the OCT imaging apparatus 300 at the target location. Inone embodiment, the OCT beam of the integrated surgical system has aresolution of no more than 5 μm.

Likewise, the surgical laser beam provided by the femtosecond lasersource 200 may be delivered to targeted locations with severalmicrometer accuracy. The resolution of the laser beam is the spatialdimension of the smallest feature at the target location that can bemodified by the laser beam without significantly affecting surroundingocular tissue. It is determined mostly by the wavelength of the laserbeam, the quality of the optics delivering the laser beam to targetlocation in the eye, the numerical aperture of the laser beam, theenergy of the laser pulses in the laser beam and the spatial resolutionof the laser scanning system at the target location. In addition, tominimize the threshold energy of the laser for photo-disruptiveinteraction, the size of the laser spot should be no more thanapproximately 5 μm.

For practical embodiments, beam conditioning, scanning and combining theoptical paths are certain functions performed on the laser beam 201, theOCT beam 301, the illumination beam 401, and the aiming beams of light451 a, 451 b. Implementation of those functions may happen in adifferent order than what is indicated in FIG. 7 . Specific opticalhardware that manipulates the beams to implement those functions canhave multiple arrangements with regards to how the optical hardware isarranged. They can be arranged in a way that they manipulate individualoptical beams separately, in another embodiment one component maycombine functions and manipulates different beams. For example, a singleset of scanners can scan both the laser beam 201 and the OCT beam 301.In this case, separate beam conditioners set the beam parameters for thelaser beam 201 and the OCT beam 301, then a beam combiner combines thetwo beams for a single set of scanners to scan the beams. While manycombinations of optical hardware arrangements are possible for theintegrated surgical system, the following section describes in detail anexample arrangement.

Beam Delivery

In the following description, the term beam may—depending on thecontext—refer to one of a laser beam, an OCT beam, an illumination beam,or one or more aiming beams. A combined beam refers to two or more of alaser beam, an OCT beam, an illumination beam, or an aiming beam thatare either collinearly combined or non-collinearly combined. Examplecombined beams include a combined OCT/laser beam, which is a collinearor non-colinear combination of an OCT beam and a laser beam, and acombined OCT/laser/illumination beam, which is a collinear ornon-collinear combination of an OCT beam, a laser beam, and anillumination beam, and a combined OCT/laser/illumination/aiming beam,which is a collinear or non-collinear combination of an OCT beam, alaser beam, an illumination beam, and one or more aiming beams. In acollinearly combined beam, the different beams may be combined bydichroic or polarization beam splitters, and delivered along a sameoptical path through a multiplexed delivery of the different beams. In anon-collinear combined beam, the different beams are delivered at thesame time along different optical paths that are separated spatially orby an angle between them.

In the description to follow, any of the foregoing beams or combinedbeams may be generically referred to as a light beam. The terms distaland proximal may be used to designate the direction of travel of a beam,or the physical location of components relative to each other within theintegrated surgical system. The distal direction refers to a directiontoward the eye; thus an OCT beam output by the OCT imaging apparatusmoves in the distal direction toward the eye. The proximal directionrefers to a direction away from the eye; thus an OCT return beam fromthe eye moves in the proximal direction toward the OCT imagingapparatus.

Referring to FIG. 8 , in one embodiment, an integrated surgical systemis configured to deliver each of a laser beam 201, an illumination beam401, and a pair of aiming beams of light 451 a, 451 b in the distaldirection toward an eye 1, and receive an illumination return beam 401back from the eye 1. In another embodiment, an integrated surgicalsystem is configured to deliver each of a laser beam 201, an OCT beam301, an illumination return beam 401, and a pair of aiming beams oflight 451 a, 451 b in the distal direction toward an eye 1, and receiveeach of an OCT return beam 301 and an illumination return beam 401 backfrom the eye 1.

In another embodiment, an integrated surgical system is configured todeliver each of a laser beam 201 and an illumination beam 401 in thedistal direction toward an eye 1, and receive an illumination returnbeam 401 and a second harmonic light beam 461 back from the eye 1. Inanother embodiment, an integrated surgical system is configured todeliver each of a laser beam 201, an OCT beam 301, and an illuminationreturn beam 401 in the distal direction toward an eye, and receive eachof an OCT return beam 301, an illumination return beam 401, and a secondharmonic light beam 461 back from the eye.

In another embodiment, an integrated surgical system is configured todeliver each of a laser beam 201, an illumination beam 401, a pair ofaiming beams of light 451 a, 451 b, in the distal direction toward aneye 1, and receive an illumination return beam 401 and a second harmoniclight beam 461 back from the eye 1. In another embodiment, an integratedsurgical system is configured to deliver each of a laser beam 201, anOCT beam 301, an illumination beam 401, and a pair of aiming beams oflight 451 a, 451 b in the distal direction toward an eye 1, and receiveeach of an OCT return beam 301, an illumination return beam 401 and asecond harmonic light beam 461 back from the eye 1.

Regarding the delivery of a laser beam, a laser beam 201 output by thefemtosecond laser source 200 passes through a beam conditioner 510 wherethe basic beam parameters, beam size, divergence are set. The beamconditioner 510 may also include additional functions, setting the beampower or pulse energy and shutter the beam to turn it on or off. Afterexisting the beam conditioner 510, the laser beam 210 enters an axialscanning lens 520. The axial scanning lens 520, which may include asingle lens or a group of lenses, is movable in the axial direction 522by a servo motor, stepper motor or other control mechanism. Movement ofthe axial scanning lens 520 in the axial direction 522 changes the axialdistance of the focus of the laser beam 210 at a focal point.

In a particular embodiment of the integrated surgical system, anintermediate focal point 722 is set to fall within, and is scannable in,the conjugate surgical volume 721, which is an image conjugate of thesurgical volume 720, determined by the focusing objective 700. Thesurgical volume 720 is the spatial extent of the region of interestwithin the eye where imaging and surgery is performed. For glaucomasurgery, the surgical volume 720 is the vicinity of the irido-cornealangle 13 of the eye.

A pair of transverse scanning mirrors 530, 532 rotated by a galvanometerscanner scan the laser beam 201 in two essentially orthogonaltransversal directions, e.g., in the x and y directions. Then the laserbeam 201 is directed towards a dichroic or polarization beam splitter540 where it is reflected toward a beam combining mirror 601 configuredto combine the laser beam 201 with an OCT beam 301.

Regarding delivery of an OCT beam, an OCT beam 301 output by the OCTimaging apparatus 300 passes through a beam conditioner 511, an axiallymoveable focusing lens 521 and a transversal scanner with scanningmirrors 531 and 533. The focusing lens 521 is used set the focalposition of the OCT beam in the conjugate surgical volume 721 and thereal surgical volume 720. The focusing lens 521 is not scanned forobtaining an OCT axial scan. Axial spatial information of the OCT imageis obtained by Fourier transforming the spectrum of theinterferometrically recombined OCT return beam 301 and reference beams302. However, the focusing lens 521 can be used to re-adjust the focuswhen the surgical volume 720 is divided into several axial segments.This way the optimal imaging spatial resolution of the OCT image can beextended beyond the Rayleigh range of the OCT signal beam, at theexpense of time spent on scanning at multiple ranges.

Proceeding in the distal direction toward the eye 1, after the scanningmirrors 531 and 533, the OCT beam 301 is combined with the laser beam201 by the beam combiner mirror 601. The OCT beam 301 and laser beam 201components of the combined laser/OCT beam 550 are multiplexed and travelin the same direction to be focused at an intermediate focal point 722within the conjugate surgical volume 721. After having been focused inthe conjugate surgical volume 721, the combined laser/OCT beam 550propagates to a second beam combining mirror 602 where it is combinedwith illumination beam 401 to form a combined laser/OCT/illuminationbeam 701. Regarding delivery of the illumination beam 401 and the pairof aiming beams of light 451 a, 451 b, details of the delivery of thesebeams is described in U.S. patent application Ser. No. 16/781,770,titled “System and Method for Locating a Surface of Ocular Tissue forGlaucoma Surgery Based on Dual Aiming Beams,” which is herebyincorporated by reference.

The combined laser/OCT/illumination/aiming beam 701 traveling in thedistal direction then passes through an objective lens 750 included inthe focusing objective 700, is reflected by a beam-folding mirror 740and then passes through an exit lens 710 and a window 801 of a patientinterface, where the intermediate focal point 722 of the laser beamwithin the conjugate surgical volume 721 is re-imaged into a focal pointin the surgical volume 720. The focusing objective 700 re-images theintermediate focal point 722, through the window 801 of a patientinterface, into the ocular tissue within the surgical volume 720.

A scattered OCT return beam 301 from the ocular tissue travels in theproximal direction to return to the OCT imaging apparatus 300 along thesame paths just described, in reverse order. The reference beam 302 ofthe OCT imaging apparatus 300, passes through a reference delay opticalpath and return to the OCT imaging apparatus from a moveable mirror 330.The reference beam 302 is combined interferometrically with the OCTreturn beam 301 on its return within the OCT imaging apparatus 300. Theamount of delay in the reference delay optical path is adjustable bymoving the moveable mirror 330 to equalize the optical paths of the OCTreturn beam 301 and the reference beam 302. For best axial OCTresolution, the OCT return beam 301 and the reference beam 302 are alsodispersion compensated to equalize the group velocity dispersion withinthe two arms of the OCT interferometer.

When the combined laser/OCT/illumination/aiming beam 701 is deliveredthrough the cornea 3 and the anterior chamber 7, the combined beampasses through posterior and anterior surface of the cornea at a steepangle, far from normal incidence. These surfaces in the path of thecombined laser/OCT/illumination/aiming beam 701 create excessiveastigmatism and coma aberrations that need to be compensated for.

With reference to FIGS. 9A and 9B, in an embodiment of the integratedsurgical system 1000, optical components of the focusing objective 700and patient interface 800 are configured to minimize spatial andchromatic aberrations and spatial and chromatic distortions. FIG. 9Ashows a configuration when both the eye 1, the patient interface 800 andthe focusing objective 700 all coupled together. FIG. 9B shows aconfiguration when both the eye 1, the patient interface 800 and thefocusing objective 700 all detached from one another.

The patient interface 800 optically and physically couples the eye 1 tothe focusing objective 700, which in turn optically couples with otheroptic components of the integrated surgical system 1000. The patientinterface 800 serves multiple functions. It immobilizes the eye relativeto components of the integrated surgical system; creates a sterilebarrier between the components and the patient; and provides opticalaccess between the eye and the instrument. The patient interface 800 isa sterile, single use disposable device and it is coupled detachably tothe eye 1 and to the focusing objective 700 of the integrated surgicalsystem 1000.

The patient interface 800 includes a window 801 having an eye-facing,concave surface 812 and an objective-facing, convex surface 813 oppositethe concave surface. The window 801 thus has a meniscus form. Withreference to FIG. 9C, the concave surface 812 is characterized by aradius of curvature r_(e), while the convex surface 813 is characterizedby a radius of curvature r_(w). The concave surface 812 is configured tocouple to the eye, either through a direct contact or through indexmatching material, liquid or gel, placed in between the concave surface812 and the eye 1. The window 801 may be formed of glass and has arefractive index n_(w). In one embodiment, the window 801 is formed offused silica and has a refractive index n_(w) of 1.45. Fused silica hasthe lowest index from common inexpensive glasses. Fluoropolymers such asthe Teflon AF are another class of low index materials that haverefractive indices lower than fused silica, but their optical quality isinferior to glasses, and they are relatively expensive for high volumeproduction. In another embodiment the window 801 is formed of the commonglass BK7 and has a refractive index n_(w) of 1.50. A radiationresistant version of this glass, BK7G18 from Schott AG, Mainz, Germany,allows gamma sterilization of the patient interface 800 without thegamma radiation altering the optical properties of the window 801.

Returning to FIGS. 9A and 9B, the window 801 is surrounded by a wall 803of the patient interface 800 and an immobilization device, such as asuction ring 804. When the suction ring 804 is in contact with the eye1, an annular cavity 805 is formed between the suction ring and the eye.When vacuum applied to the suction ring 804 and the cavity via a vacuumtube a vacuum pump (not shown in FIGS. 9A and 9B), vacuum forces betweenthe eye and the suction ring attach the eye to the patient interface 800during surgery. Removing the vacuum releases or detach the eye 1.

The end of the patient interface 800 opposite the eye 1 includes anattachment interface 806 configured to attach to the housing 702 of thefocusing objective 700 to thereby affix the position of the eye relativeto the other components of the integrated surgical system 1000. Theattachment interface 806 can work with mechanical, vacuum, magnetic orother principles and it is also detachable from the integrated surgicalsystem.

The focusing objective 700 includes an aspheric exit lens 710 having aneye-facing, concave surface 711 and a convex surface 712 opposite theconcave surface. The exit lens 710 thus has a meniscus form. While theexit lens 710 shown in FIGS. 9A and 9B is an aspheric lens giving moredesign freedom, in other configurations the exit lens may be a sphericallens. Alternatively, constructing the exit lens 710 as a compound lens,as opposed to a singlet, allows more design freedom to optimize theoptics while preserving the main characteristics of the optical systemas presented here. With reference to FIG. 9C, the concave surface 711 ischaracterized by a radius of curvature r_(y), while the convex surface712 is characterized by an aspheric shape. The aspheric convex surface712 in combination with the spherical concave surface 711 result in anexit lens 710 having varying thickness, with the outer perimeter edges715 of the lens being thinner than the central, apex region 717 of thelens. The concave surface 711 is configured to couple to the convexsurface 813 of the window 801. In one embodiment, the exit lens 710 isformed of fused silica and has a refractive index n_(x) of 1.45.

Minimally Invasive Surgical Treatments

FIG. 10 is a three-dimensional schematic illustration of anatomicalstructures of the eye relevant to the surgical treatment enabled by theintegrated surgical system 1000. To reduce the IOP, laser treatmenttargets ocular tissues that affect the trabecular outflow pathway 40.These ocular tissues may include the trabecular meshwork 12, the scleralspur 14, the Schlemm's canal 18, and the collector channels 19. Thetrabecular meshwork 12 has three layers, the uveal 15, the corneoscleralmeshwork 16, and the juxtacanalicular tissue 17. These layers are porousand permeable to aqueous, with the uveal 15 being the most porous andpermeable, followed by the corneoscleral meshwork 16. The least porousand least permeable layer of the trabecular meshwork 12 is thejuxtacanalicular tissue 17. The inner wall 18 a of the Schlemm's canal18, which is also porous and permeable to aqueous, has characteristicssimilar to the juxtacanalicular tissue 17.

FIG. 11 includes a three-dimensional illustration of a treatment patternP1 to be applied by the integrated surgical system 1000 to affect thesurgical volume 900 of ocular tissue shown in FIG. 10 , and atwo-dimensional schematic illustration of the treatment pattern P1overlaying anatomical structures to be treated. FIG. 12 is athree-dimensional schematic illustration of the anatomical structures ofthe eye including an opening 902 through the that results from theapplication of the laser treatment pattern of FIG. 11 . The opening 902provides and outflow pathway 40 that reduces the flow resistance in theocular tissue to increase aqueous flow from the anterior chamber 7 intothe Schlemm's canal 18 and thereby reduce the IOP of the eye.

Surgical treatments reduce outflow pathway resistance while minimizingocular tissue modification through design and selection of lasertreatment patterns. A treatment pattern is considered to define acollection of a laser-tissue interaction volumes, referred to herein ascells. The size of a cell is determined by the extent of the influenceof the laser-tissue interaction. When the laser spots, or cells, arespaced close along a line, the laser creates a narrow, microscopicchannel. A wider channel can be created by closely spacing a multitudeof laser spots within the cross section of the channel. The arrangementof the cells may resemble the arrangement of atoms in a crystalstructure.

With reference to FIG. 11 , a treatment pattern P1 may be in the form ofa cubic structure that encompasses individual cells arranged inregularly spaced rows, columns and sheets or layers. The treatmentpattern P1 may be characterized by x, y, z dimensions, with x, y, zcoordinates of the cells being calculated sequentially from neighbor toneighbor in the order of a column location (x coordinate), a rowlocation (y coordinate), and a layer location (z coordinate). Atreatment pattern P1 as such, defines a three-dimensional model ofocular tissue to be modified by a laser or a three-dimensional model ofocular fluid to be affected by a laser.

A treatment pattern P1 is typically defined by a set of surgicalparameters. The surgical parameters may include one or more of atreatment area A that represents a surface area or layer of oculartissue through which the laser will travel. The treatment area A isdetermined by the treatment height, h, and the lateral extent of thetreatment, w. A treatment thickness t that represents the level to whichthe laser will cut into the ocular tissue from the distal extent orborder of the treatment volume at or near Schlemm's canal 18 to theproximal extent or border at or near the surface of the trabecularmeshwork 12. Thus, a laser applied in accordance with a treatmentpattern may affect or produce a surgical volume that resembles thethree-dimensional model of the treatment pattern, or may affect fluidlocated in an interior of an eye structure resembled by thethree-dimensional model. In one example, a treatment pattern P1 may havea lateral or circumferential extent, w=1000 μm, a height, h=200 μm, anda thickness, t=500 μm.

Additional surgical parameters define the placement of the surgicalvolume or affected volume within the eye. For example, with reference toFIGS. 10 and 11 , placement parameters may include one or more of alocation 1 that represents where the treatment is to occur relative tothe circumferential angle of the eye, and a treatment depth d thatrepresents a position of the three-dimensional model of ocular tissue orocular fluid within the eye relative to a reference eye structure. Inthe following, the treatment depth d is shown and described relative tothe region where the anterior chamber 7 meets the trabecular meshwork12. Together, the treatment pattern and the placement parameters definea treatment plan.

A femtosecond laser provides highly localized, non-thermalphoto-disruptive laser-tissue interaction with minimal collateral damageto surrounding ocular tissue. Photo-disruptive interaction of the laseris utilized in optically transparent tissue. The principal mechanism oflaser energy deposition into the ocular tissue is not by absorption butby a highly nonlinear multiphoton process. This process is effectiveonly at the focus of the pulsed laser where the peak intensity is high.Regions where the beam is traversed but not at the focus are notaffected by the laser. Therefore, the interaction region with the oculartissue is highly localized both transversally and axially along thelaser beam.

With reference to FIGS. 10 and 11 , in accordance with embodimentsdisclosed herein a surgical volume 900 of ocular tissue to be treated isidentified by the integrated surgical system 1000 and a treatmentpattern P1 corresponding to the surgical volume is designed by theintegrated surgical system. Alternatively, the treatment pattern P1 maybe designed first, and then an appropriate surgical volume 900 forapplying the treatment pattern may be identified. The surgical volume900 of ocular tissue may comprise portions of the trabecular meshwork 12and the Schlemm's canal 18. For example, the surgical volume 900 ofocular tissue shown in FIG. 11 includes portions of the uveal 15, thecorneoscleral meshwork 16, the juxtacanalicular tissue 17, and the innerwall 18 a of the Schlemm's canal 18. The treatment pattern P1 defines alaser scanning procedure whereby a laser is focused at different depthlocations in ocular tissue and then scanned in multiple directions toaffect a three-dimensional volume of tissue comprising multiple sheetsor layers of affected tissue.

With reference to FIGS. 11 and 12 , during a laser scanning procedure, asurgical laser 701 may scan ocular tissue in accordance with thetreatment pattern P1 to form an opening 902 that extends from theanterior chamber 7, through each of the uveal 15, the corneoscleralmeshwork 16, the juxtacanalicular tissue 17 of the trabecular meshwork12, and the inner wall 18 a of the Schlemm's canal 18. While the exampleopening 902 in FIG. 12 is depicted as a continuous, single lumendefining a fluid pathway, the opening may be defined an arrangement ofadjacent pores forming a sponge like structure defining a fluid pathwayor a combination thereof. While the example opening 902 in FIG. 12 is inthe shape of a cube, the opening may have other geometric shapes.

The movement of the laser as it scans to affect the surgical volume 900follows the treatment pattern P1, which is defined by a set of surgicalparameters that include a treatment area A and a thickness t. Thetreatment area A is defined by a width w and a height h. The width maybe defined in terms of a measure around the circumferential angle. Forexample, the width w may be defined in terms of an angle, e.g., 90degrees, around the circumferential angle.

Referring to FIGS. 10 and 11 , an initial placement of the laser focuswithin the eye is defined by a set of placement parameters, including adepth d and a location l. The location l defines a point around thecircumferential angle of the eye at which laser treatment will begin,while the depth d defines a point between the anterior chamber 7 and theSchlemm's canal 18 where the laser treatment begins or ends. The depth dis measured relative to the region where the anterior chamber 7 meetsthe trabecular meshwork 12. Thus, a first point that is closer to theSchlemm's canal 18 side of the trabecular meshwork 12 may be describedas being deeper than a second point that is closer to the anteriorchamber 7 side of the trabecular meshwork 12. Alternatively, the secondpoint may be described as being shallower than the first point.

With reference to FIG. 12 , the opening 902 resulting from laserapplication of the treatment pattern P1 resembles the surgical volume900 and is characterized by an area A and thickness t similar to thoseof the surgical volume and the treatment pattern. The thickness t of theresulting opening 902 extends from the anterior chamber 7 and throughthe inner wall 18 a of the Schlemm's canal 18, while the area A definesthe cross-section size of the opening 902.

In accordance with embodiments disclosed herein, during a laser scanningprocedure, a laser focus is moved to different depths d in ocular tissueand then scanned in two lateral dimensions or directions as defined by atreatment pattern P1 to affect a three-dimensional volume 900 of oculartissue comprising multiple sheets or layers of affected tissue. The twolateral dimensions are generally orthogonal to the axis of movement ofthe laser focus. With reference to FIG. 12 , the movement of a laserfocus during laser scanning is described herein with reference to x, y,and z directions or axes, wherein: 1) movement of the laser focus todifferent depths d through the thickness t of treatment pattern P1 orthe volume 900 of tissue corresponds to movement of the focus along thez axis, 2) movement of the laser focus in two dimensions or directionsorthogonal to the z axis corresponds to movement of the laser focusalong the width w of the treatment pattern P1 or the volume 900 oftissue in the x direction, and movement of the laser focus along theheight h of the treatment pattern P1 or the volume 900 of tissue in they direction.

As used herein scanning of the laser focus generally corresponds to araster type movement of the laser focus in the x direction, the ydirection, and the z direction. The laser focus may be located at apoint in the z direction and then raster scanned in two dimensions ordirections, in the x direction and the y direction. The focal point ofthe laser in the z direction may be referred to as a depth d within thetreatment pattern P1 or the volume 900 of tissue. The two-directionraster scanning of the laser focus defines a layer of laser scanning,which in turn produces a layer of laser-affected tissue.

During laser scanning, pulse shots of a laser are delivered to tissuewithin the volume of ocular tissue corresponding to the treatmentpattern P1. Because the laser interaction volume is small, on the orderof a few micrometers (m), the interaction of ocular tissue with eachlaser shot of a repetitive laser breaks down ocular tissue locally atthe focus of the laser. Pulse duration of the laser for photo-disruptiveinteraction in ocular tissue can range from several femtoseconds toseveral nanoseconds and pulse energies from several nanojoules to tensof microjoules. The laser pulses at the focus, through multiphotonprocesses, breaks down chemical bonds in the molecules, locallyphoto-dissociate tissue material and create gas bubbles in wet tissue.The breakdown of tissue material and mechanical stress from bubbleformation fragments the tissue and create clean continuous cuts when thelaser pulses are laid down in proximity to one another along geometricallines and surfaces.

Table 1 includes examples of treatment pattern parameters and surgicallaser parameters for treating tissue. The range of the parameter set islimited by practical ranges for the repetition rate of the laser and thescanning speed of the scanners.

TABLE 1 Treatment pattern dimensions Opening Cell size Laser Laser Laserw[mm], cross w[μm], average repetition pulse Procedure Tissue h[mm],section A h[μm], power rate energy time treated t[mm] [mm²] t[μm] [W][kHz] [μJ] [s] Trabecular 1.5, 0.2, 0.2 0.3 3, 3, 3 0.9 300 3 7.4meshwork Trabecular 2, 0.2, 0.2 0.4 4, 4, 4 1 200 5 6.3 meshwork

Alignment and Diagnostic Device

FIG. 13 is a block diagram of an alignment and diagnostic device 1300for visualizing an irido-corneal angle 13 of an eye 1. FIGS. 14A and 14Bare schematic illustrations of the alignment and diagnostic device 1300.The device 1300 includes an optics structure 1302 and an imagingapparatus 1306. The optics structure 1302 is configured to engage with apatient interface 800 placed on the eye 1 to provide a line of sight1304 in the direction of the irido-corneal angle 13, and to subsequentlydisengage from the patient interface. The imaging apparatus 1306 isassociated with the optics structure 1302 and has at least one imagingcomponent aligned with the line of sight 1304 to enable capturing animage of the eye 1 including the irido-corneal angle 13. The imagingcomponent may be a camera 1308, an OCT component 1330 of an OCT imagingapparatus 300, a dual aiming beam apparatus 1332, or a second harmoniclight detection apparatus 1334.

With reference to FIGS. 14A and 14B, the optics structure 1302 includesone or more facet mirrors 1310 that provide a view of the irido-cornealangle 13 through an exit lens 1312 of the optics structure. In oneconfiguration, the exit lens 1312 is an aspheric exit lens having aneye-facing, concave surface 1314 and a convex surface 1316 opposite theconcave surface. The exit lens 1312 thus has a meniscus form. Similar tothe exit lens 710 shown in FIGS. 9A and 9B, the exit lens 1312 of theoptics structure 1302 may be an aspheric lens giving more designfreedom, in other configurations the exit lens may be a spherical lens.Similar to the exit lens 710 shown in FIGS. 9A and 9B, the exit lens1312 of the optics structure 1302 may have a concave surface 1314characterized by a radius of curvature r_(y), while the convex surface1316 is characterized by an aspheric shape. The aspheric convex surface1316 in combination with the spherical concave surface 1314 result in anexit lens 1312 having varying thickness, with the outer perimeter edgesof the lens being thinner than the central, apex region of the lens. Theconcave surface 1314 is configured to couple to the convex surface 813of the window 801.

While the optics structure 1302 illustrated in FIGS. 14A and 14B has asingle facet mirror 1310, additional facet mirrors may be included toprovide images of the eye around a larger portion of the circumferentialextent of the irido-corneal angle. Accordingly, in some configurations,the optics structure 1302 may be configured to provide the line of sight1304 in the direction of the irido-corneal angle 13 around a smallportion of the circumferential extent of the irido-corneal angle. Forexample, FIG. 15A is an illustration of an image 1502 of acircumferential extent 1504 of an irido-corneal angle of an eye capturedby an optics structure 1302 having a single facet mirror 1506. Thesingle facet mirror configuration provides a line of sight in thedirection of the irido-corneal angle at the circumferential extent 1504opposite the single facet mirror 1506.

In other configurations, the optics structure 1302 may be configured toprovide lines of sight 1304 in the direction of the irido-corneal angle13 around a larger circumferential extent of the irido-corneal angle.For example, FIG. 15B is an illustration of four images 1508, 1510,1512, 1514 of portions of an irido-corneal angle 13 captured by anoptics structure 1302 having four facet mirrors (not shown). Each facetmirror provides a line of sight in the direction of the irido-cornealangle at a portion of the circumferential extent 1516 opposite the facetmirror.

Returning to FIGS. 13, 14A and 14B, in one embodiment of the alignmentand diagnostic device 1300 the imaging apparatus 1306 is a visualobservation apparatus, e.g., a camera 1308. The camera 1308 includes anillumination source 1326 configured to output light 401 in the directionof the line of sight into the irido-corneal angle 13. The camera 1308further includes a focusing optics and magnifier 1324 configured tofocus and magnify the image captured by the camera. The camera 1306 mayalso include a display 1328 for displaying an image captured by thecamera. FIG. 16 is an example image 1600 of a portion of anirido-corneal angle captured by a camera 1306 together with a surgicaloverlay mark 1602. The surgical overlay mark 1602 may correspond to anarea that may be treated by the surgical laser of the integratedsurgical system 1000.

In another embodiment of the alignment and diagnostic device 1300 theimaging apparatus 1306 is configured to be coupled to an OCT imagingapparatus 300 remote from the alignment and diagnostic device 1300 andincludes one or more OCT components 1330. The one or more OCT components1330 may be, for example, an OCT scanner head and an interfaceconfigured to couple the OCT scanner head to the remote OCT imagingapparatus 300 and to receive an OCT beam 301 from the apparatus. Theremote OCT apparatus 300 may be part of an integrated surgical system1000, which may include a display for displaying OCT images. FIGS. 17Aand 17B are example images 1700, 1706 of a portion of an irido-cornealangle captured by the one or more OCT components 1330 in conjunctionwith the OCT imaging apparatus 300 showing the Schlemm's canal 1702 andtrabecular meshwork 1704 from different OCT scan directions. These typesof images may be used to locate a target surface of ocular tissue notvisible in an image captured by a camera. For example, with reference toFIG. 11 , target tissue of the trabecular meshwork 12 at a depth dbetween the anterior chamber 7 and the Schlemm's canal 18 may be visiblein an OCT image.

In another embodiment of the alignment and diagnostic device 1300 theimaging apparatus 1306 includes a dual aiming beam mechanism 1332 andoptics configured to transmit a first beam of light 451 a at a firstwavelength and a second beam light 451 b at a second wavelengthdifferent then the first wavelength in the direction of the line ofsight into the irido-corneal angle 13. In one configuration, the dualaiming beam mechanism 1332 includes one or more fiber optic cables.Spots generated by a first beam of light and a second beam of light maybe used to locate a surface of ocular tissue as disclosed in U.S. patentapplication Ser. No. 16/781,770, titled “System and Method for Locatinga Surface of Ocular Tissue for Glaucoma Surgery Based on Dual AimingBeams.” These spots may be displayed on a display, such as the display1328 of the camera 1308, or a display remote from the alignment anddiagnostic device 1300, and may be used to locate a target surface ofocular tissue not visible in an image captured by a camera. For example,with reference to FIG. 11 , a target surface corresponding to thesurface of the uveal 15 facing the anterior chamber 7 may be locatedusing the dual aiming beam apparatus.

In another embodiment of the alignment and diagnostic device 1300 theimaging apparatus 1306 includes a second harmonic light detectionapparatus 1334. The second harmonic light detection apparatus 1334generates information indicative of the presence or absence of secondharmonic light in the irido-corneal angle of the eye that may begenerated by an encounter between the focus of a laser beam 201 andocular tissue. To this end, in one embodiment, the second harmonic lightdetection apparatus 1334 is configured to detect for a second harmoniclight beam 1336 using a photodetector, and to provide an intensityprofile of second harmonic generated light. The intensity of secondharmonic generated light may be used to locate a surface of oculartissue as disclosed in U.S. patent application Ser. No. 16/723,883,titled “System and Method for Locating a Structure of Ocular Tissue forGlaucoma Surgery Based on Second Harmonic Light.” The second harmoniclight may be displayed on a display, such as the display 1328 of thecamera 1308, or a display remote from the alignment and diagnosticdevice 1300, and may be used to locate a target surface of ocular tissuenot visible in an image captured by a camera. For example, withreference to FIG. 11 , target tissue between the anterior chamber 7 andthe Schlemm's canal 18 may be located using the second harmonic lightdetection apparatus 1334.

FIGS. 18A, 18B and 18C are illustrations of a first embodiment of analignment and diagnostic device 1300 for visualizing an irido-cornealangle 13 of an eye 1. In this embodiment, the imaging apparatus 1306 andthe optics structure 1302 are assembled together to form the alignmentand diagnostic device 1300. For example, the imaging apparatus 1306 andthe optics structure 1302 may mechanically couple together through abayonet-style mount or a screw mechanism. In this configuration, theimaging apparatus 1306 and the optics structure 1302 may decouple fromeach other as need to, for example, if either requires replacement. Inan alternate configuration, the imaging apparatus 1306 and the opticsstructure 1302 are fixedly secured together such that the alignment anddiagnostic device 1300 is a single unitary structure and the componentparts cannot be separated.

The optics structure 1302 is configured to mechanically couple to thepatient interface 800 and to rotate relative to the patient interfacetogether with the at least one imaging apparatus 1306 to enable thecapturing of images of the irido-corneal angle 13 at various angularpositions around the circumferential extent of the irido-corneal angle.To this end, and with additional reference to FIG. 14A, the patientinterface 800 includes a wall 803 around the window 801 that defines aninterior space 807 and the optics structure 1302 is configured to matewithin the interior space. The interior space 807 of the patientinterface 800 is characterized by an interior shape and the opticsstructure 1302 is characterized by an exterior shape similar to theinterior shape. In other words, the optics structure 1302 has a formfactor that fits into the patient interface 800. Furthermore, the opticsstructure 1302 is characterized by an exterior surface 1318 that enablesrotation of the optics structure relative to the patient interface 800about a symmetry axis 1320 extending through the optics structure andthe patient interface.

With reference to FIG. 18A, the optics structure 1302 comprises amechanism for providing a measure of the relative angular positionbetween the optics structure and the patient interface 800. Themechanism may be a rotational registration 1802 that includes a severalalignment marks 1804 spaced apart around the circumference of thehousing 1806 of the optics structure 1302. The marks 1804 provide anangular scale configured to align with an alignment mark 1808 of thepatient interface 800. During use of the alignment and diagnostic device1300 the optics structure 1302 together with the imaging apparatus 1306may be rotated relative to the patient interface 800 to obtain an imageof the desired portion of the circumferential extent of theirido-corneal angle of the eye, and then rotated to another position toobtain an image of another portion of the circumferential extent of theirido-corneal angle of the eye. Rotation is particularly needed when theoptics structure 1302 is configured with a single facet mirror, such asdescribed above with reference to FIG. 14A. Upon capture of the desiredimage, the position of the alignment marks 1804 relative to an alignmentmark 1808 of the patient interface may be recorded as a “circumferentialangular position” and subsequently used to align the focusing objective700 of the integrated surgical system 1000 relative to the patientinterface 800 during a surgical procedure.

With reference to FIGS. 14A and 14B, the alignment and diagnostic device1300 includes a locking mechanism 1322 associated with the opticsstructure 1302. The locking mechanism 1322 is configured to enablefixation of the optics structure 1302 relative to the patient interface800 at various angular positions around the circumferential extent ofthe irido-corneal angle 13. To this end, the locking mechanism 1322 isconfigured to engage the attachment interface 806 of the patientinterface 800. The locking mechanism 1322 may be anyone of: a vacuumport coupled to a vacuum source that establishes a vacuum betweensurfaces of the optics structure and the patient interface, a mechanicalstructure configured to engage a complimentary mechanical structure 806of the patient interface (e.g., a bayonet mount, a mating flange,locking clips), a magnetic structure coupled to a magnetic source thatestablishes a magnetic force between the magnetic structure and amagnetic structure 806 of the patient interface (e.g., electromagnet onoptics structure and ferromagnetic insert on patient interface), and apneumatic element coupled to a pneumatic source, wherein the pneumaticelement is configured to expand against a surface of the patientinterface.

Having thus described the structure and configuration of an alignmentand diagnostic device 1300, a method of laser surgical treatment of aneye 1 that employs the device is disclosed with reference to FIGS. 21Aand 21B. The method aligns a patient interface 800 relative to a targetsurgical location of the eye 1 using the alignment and diagnostic device1300 so that a laser output by a surgical system 1000 subsequentlycoupled to the patient interface is directed to the target surgicallocation.

With reference to FIGS. 21A and 21B, at block 2102, the integratedsurgical system 1000 is prepared for surgery. Such preparation includesentering patient and pre-op data and a surgical plan, as necessary. Thesurgical plan may include, for example, a treatment plan in the form of3D CAD software file, a stereo lithography file, an image file, aplurality of image files, an spreadsheet file, or parameter valuespre-entered by the surgeon.

At block 2104, the patient is prepared for surgery. Such preparationincludes placing the patient on a surgical bed in supine position;applying topical anesthetic eye drops as necessary; and applyinglubricant on the eye 1 as necessary.

At block 2106, and with reference to FIGS. 18A and 18B, an alignment anddiagnostic device 1300 is inserted into a patient interface 800. Notethat the locking mechanism 1322 of the alignment and diagnostic device1300 shown in FIG. 14B may or may not be engaged with the patientinterface 800 at this point. In cases where the alignment and diagnosticdevice 1300 is locked to the patient interface 800 by the lockingmechanism 1322, the device and interface move together and in effect,become a single combined structure. In cases where the alignment anddiagnostic device 1300 is not locked to the patient interface 800 by thelocking mechanism 1322, the friction fit between the alignment anddiagnostic device 1300 and the patient interface 800 may be sufficientto make the combination of the device and interface stable enough tomove together like a single structure.

In either case, at block 2108, and with reference to FIG. 18C, thecombination of the alignment and diagnostic device 1300 and the patientinterface 800 is brought into contact with the eye 1. Note that theimmobilization device 804 of the patient interface 800 shown in FIG. 14Bis not engaged at this point to allow for movement of the alignment anddiagnostic device 1300 together with the patient interface relative tothe eye 1.

At block 2110, and with reference to FIG. 19A, an image 1900 of theirido-corneal angle 13 is captured by the imaging apparatus 1306 of thealignment and diagnostic device 1300 and displayed for observation bythe user. In one embodiment, the image 1900 may be captured by a camera1308 and presented on a display 1328 of the alignment and diagnosticdevice 1300. The display 1328 is configured to display a surgicaloverlay mark 1902 to assist in aligning the alignment and diagnosticdevice 1300 and patient interface 800 relative to a target surgicallocation 1909 at a circumferential extent of the irido-corneal angle.

In one configuration, the surgical overlay mark 1902 includes: A) acoarse surgical area (CSA) 1901 that defines a coarse area that may betreated by the surgical laser of the integrated surgical system 1000; B)a fine surgical area (FSA) overlay 1903 that defines a more fine areathat can be treated by the surgical laser of the integrated surgicalsystem 1000; C) a circumference scanning mark 1905 that indicates thelength and orientation of circumferential scanning by the OCT imagingapparatus 300 coupled to the alignment and diagnostic device; and D) atransverse or azimuthal scanning mark 1907 that indicates the length andorientation of the azimuthal scanning by the OCT imaging apparatus.

The coarse surgical area overlay 1901 and the fine surgical area overlay1903 seen in the alignment and diagnostic device 1300 are made tocoincide with the coarse surgical area and the fine surgical area of thesurgical laser of the integrated surgical system 1000 by scaling therelative size of the overlay areas according to the relativemagnification of the alignment and diagnostic device and themagnification of the integrated surgical system 1000. Similarly, thecircumference scanning mark 1905 and the azimuthal scanning mark 1907seen in the alignment and diagnostic device 1300 are made to coincidewith the circumference scanning mark and the azimuthal scanning mark ofthe OCT imaging apparatus 300 by scaling the relative size of the marksaccording to the relative magnification of the alignment and diagnosticdevice and the magnification of the integrated surgical system 1000.

With reference to FIGS. 19B and 19C, which are schematic representationsbased on the image of FIG. 19A, the image 1900 of the irido-cornealangle 13 captured by the imaging apparatus 1306 of the alignment anddiagnostic device 1300 displays observable anatomical features includingthe ciliary body band and iris 1904, scleral spur 1906, the cornea 1908,the trabecular meshwork 1910 and Schwalbe's line 1912. The display 1328of the alignment and diagnostic device 1300 provides the surgicaloverlay mark 1902 that includes the previously described CSA overlay1901, FSA overlay 1903, circumference scanning mark 1905, and azimuthalscanning mark 1907.

Returning to FIGS. 21A and 21B, at block 2112 and with reference to FIG.19B, while continuing to observe the image of the irido-corneal angle 13captured by the alignment and diagnostic device 1300, the combination ofthe alignment and diagnostic device and the patient interface 800 ismoved on the eye 1 to bring an image of a circumferential extent of theirido-corneal angle and a target surgical location 1909 of thetrabecular meshwork 1910 into the surgical overlay mark 1902, includingthe CSA overlay 1901. For example, with reference to FIG. 22A, thecombination of the alignment and diagnostic device 1300 and the patientinterface 800 may be moved by sliding or tilting the combination overthe cornea. The combination alignment and diagnostic device 1300together and the patient interface 800 moves relative to the eye byvirtue of the eye lubricant applied. While moving the alignment anddiagnostic device 1300 and the patient interface 800, physical contactbetween the anterior corneal surface and the patient interface ismaintained.

The target surgical location 1909 to be brough into the surgical overlaymark 1902 includes a target volume of ocular tissue to be laser treated.As mention above, the coarse surgical area overlay 1901 displayed by thealignment and diagnostic device 1300 coincides with the coarse surgicalarea of the surgical laser of the integrated surgical system 1000. Assuch, orienting the alignment and diagnostic device 1300 so that thetarget surgical location 1909 is in the CSA overlay 1901 assures thatthe target volume of ocular tissue included in that segment is in theCSA of the surgical laser. Note that the alignment and diagnostic device1300 together with the patient interface 800 will slide relative to theeye by virtue of the eye lubricant applied.

At block 2114 and with reference to FIGS. 19C and 22A, while continuingto observe the image 1900 of the irido-corneal angle 13 captured by thealignment and diagnostic device 1300, the combination of the alignmentand diagnostic device and the patient interface 800, is further movedrelative to the eye 1 as needed to bring the image of the targetsurgical location 1909 of the trabecular meshwork 1910 into asubstantially central alignment and generally parallel alignment withinthe surgical overlay mark 1902 and thus substantially within the FSAoverlay 1903. As mention above, the FSA overlay 1903 displayed by thealignment and diagnostic device 1300 coincides with the fine surgicalarea of the surgical laser of the integrated surgical system 1000. Assuch, orienting the alignment and diagnostic device 1300 so that thetarget surgical location 1909 is in the FSA overlay 1903 assures thatthe target volume of ocular tissue is in the FSA of the surgical laser.

At optional block 2116, in cases where the focus of the surgical laserof the integrated surgical system 1000 has a limited depth range, anadditional component of the alignment and diagnostic device 1300 may beused to bring one or more depth fiducials of the target surgicallocation 1909 within the depth range of the laser. For example, a dualaiming beam apparatus 1332 may be used to detect a depth fiducial, suchas the surface of the trabecular meshwork 1910 facing the anteriorchamber, as disclosed in U.S. patent application Ser. No. 16/781,770,titled “System and Method for Locating a Surface of Ocular Tissue forGlaucoma Surgery Based on Dual Aiming Beams.” The dual aiming beams ofthe apparatus form a single spot on the when the surface of thetrabecular meshwork 1910 facing the anterior chamber. The single spot iscaptured by the camera 1308 and presented on the display 1328 of thealignment and diagnostic device 1300. The single spot may be observedand the alignment and diagnostic device 1300 together with the patientinterface 800 may be slid and rotated relative to the eye to place thesingle spot, and thus the depth fiducial, i.e., the surface of thetrabecular meshwork 1910 facing the anterior chamber, within thesurgical overlay mark 1902.

In another example, an OCT imaging apparatus 300 may be used to locate adepth fiducial, such as a surface of the trabecular meshwork 1910 facingthe Schlemm's canal 1702, or a wall of the Schlemm's canal. Withreference to FIGS. 17A and 17B, one or both of a circumferential OCTscan image 1700 and an azimuthal OCT scan image 1706 of a portion of theirido-corneal angle 13 of the eye may be captured by the OCT imagingapparatus 300 using one or more OCT components 1330 of the alignment anddiagnostic device 1300 and displayed together with a surgical overlaymark 1705, 1707. In this case, the images 1700, 1706 may include theSchlemm's canal 1702, the trabecular meshwork 1704, collector channeland blood vessels. These images 1700, 1706 may be observed and thealignment and diagnostic device 1300 together with the patient interface800 may be moved relative to the eye to place the depth fiducial ofinterest, e.g., a surface of the trabecular meshwork 1910 facing theSchlemm's canal 1702, or a wall of the Schlemm's canal, within asurgical overlay mark 1705, 1707.

In yet another example, a second harmonic light detection apparatus 1334may be used to detect a depth fiducial, such as a surface of thetrabecular meshwork 1910 facing the Schlemm's canal 1702, or a wall ofthe Schlemm's canal, as disclosed in as disclosed in U.S. patentapplication Ser. No. 16/723,883, titled “System and Method for Locatinga Structure of Ocular Tissue for Glaucoma Surgery Based on SecondHarmonic Light.” The second harmonic light may be displayed on thedisplay 1328 of the camera 1308, or a display remote from the alignmentand diagnostic device 1300, and may be used to locate the depth fiducialof interest. The second harmonic light may be observed and the alignmentand diagnostic device 1300 together with the patient interface 800 maybe slid and rotated relative to the eye to place the second harmoniclight, and thus the depth fiducial of interest, e.g., a surface of thetrabecular meshwork 1910 facing the Schlemm's canal 1702, or a wall ofthe Schlemm's canal, within the surgical overlay mark 1902.

At block 2118, once the target surgical location 1909 is brough intocentral alignment with the surgical overlay mark 1902, and optionally atan acceptable depth range, the patient interface 800 is secured to theeye 1. For example, an immobilization device 804 may be activated tosecure the patient interface 800 to the eye 1.

At block 2120, the circumferential angular position of the targetsurgical location 1909 is read and recorded. For example, with referenceto FIG. 18A, the circumferential angular position may be read from therotational registration 1802 of the alignment and diagnostic device 1300that includes a several alignment marks 1804 spaced apart around thecircumference of the housing 1806 of the optics structure 1302. Thiscircumferential angular position is subsequently used to align thefocusing objective 700 of the surgical system 1000 during lasertreatment.

At this point, the process may proceed directly to block 2122.Alternatively, at block 2121 and with reference to FIG. 22B, the surgeonmay inspect the corneal angle by rotating the alignment and diagnosticdevice 1300 in the patient interface 800 with respect to the axis of theeye 1 as shown in FIG. 22B. In cases where the alignment and diagnosticdevice 1300 is locked to the patient interface 800, the device isunlocked from the patient interface prior to rotating. The patientinterface 800 is locked in place on the eye 1 and does not rotate duringmaneuver of the alignment and diagnostic device 1300. After theinspection, the process proceeds to block 2122.

At block 2122 and with reference to FIG. 18A, the alignment anddiagnostic device 1300 is removed from the patient interface 800, whilemaking sure that the patient interface 800 remains attached to the eye 1and immobilized.

At block 2124 and with reference to FIG. 20A, the integrated surgicalsystem 1000 is coupled to the patient interface 800. To this end, thepatient interface 800 and the attachment end 2002 of the integratedsurgical system 1000 are brought to proximity by moving the surgical bedor the surgical instrument. The attachment end 2002 of the integratedsurgical system 1000 includes the focusing objective 700 of theintegrated surgical system 1000. With reference to FIG. 20B, theattachment end 2002 of the surgical instrument is docked into thepatient interface 800 to thereby place the focusing objective 700 intothe patient interface. Once the attachment end 2002 of the surgicalinstrument is docked into the patient interface 800, the patientinterface is secured to the focusing objective 700 of the surgicalinstrument. The patient interface 800 may be secured by engaging theattachment interface 806 of the patient interface.

At block 2126, the circumferential angular position of the surgicalaiming of the integrated surgical system 1000 is brought to thecircumferential angular position read at block 2120 from the alignmentand diagnostic device 1300. An image captured by an imaging device,e.g., the OCT imaging apparatus 300 or the visual microscope 400, of theintegrated surgical system 1000 is displayed and observed. The targetsurgical location 1909 should be observable in the image. The imageshould correspond to the image shown is FIG. 19A, with the targetsurgical location 1909 being in substantially central alignment withinthe surgical overlay mark 1902.

At block 2128, the focus of the surgical laser beam is located relativeto the target surgical location 1909. For example, the focus may belocated at a depth fiducial corresponding to a surface of the trabecularmeshwork 1910 facing the anterior chamber, as disclosed in U.S. patentapplication Ser. No. 16/781,770, titled “System and Method for Locatinga Surface of Ocular Tissue for Glaucoma Surgery Based on Dual AimingBeams.” A focus may be placed at a depth fiducial corresponding to asurface of the trabecular meshwork 1910 facing the Schlemm's canal 1702,or a wall of the Schlemm's canal, using one or more OCT images, or asdisclosed in as disclosed in U.S. patent application Ser. No.16/723,883, titled “System and Method for Locating a Structure of OcularTissue for Glaucoma Surgery Based on Second Harmonic Light.”

At block 2130, optical energy is applied to a target volume of oculartissue at the target surgical location 1909 in accordance with atreatment pattern. For example, optical energy may be delivered byscanning a laser through a three-dimensional treatment patter to treatglaucoma, as disclosed in U.S. patent application Ser. No. 16/838,858,titled “Method, System, and Apparatus for Generating Three-DimensionalTreatment Patterns for Laser Surgery Of Glaucoma,” the disclosure ofwhich is incorporated by reference.

At block 2132, upon completion of laser treatment at the target surgicallocation 1909, the integrated surgical system 1000 is decoupled from theeye 1 and the patient interface is decoupled from the surgical system.To this end, the immobilization device 804 of the patient interface 800is disengaged to allow movement of the interface relative to the eye 1.The attachment end 2002 of the integrated surgical system 1000 is thenremoved from the proximity of the eye 1, together with the patientinterface 800. The attachment end 2002 of the integrated surgical system1000 is then removed from the patient interface 800.

At block 2134, if needed, the process returns to block 2106 and isrepeated for an additional target surgical location.

It is to be understood that the embodiments of the invention hereindescribed are merely illustrative of the application of the principlesof the invention. Reference herein to details of the illustratedembodiments is not intended to limit the scope of the claims, whichthemselves recite those features regarded as essential to the invention.

What is claimed is:
 1. A handheld device configured for handheldmovement relative to an eye for visualizing an irido-corneal angle ofthe eye, the handheld device comprising: an optics structure comprisingan optical assembly configured to optically couple with the eye and toprovide a line of sight to the irido-corneal angle when an axis of theoptics structure is aligned relative to an optical axis of the eye; andan imaging apparatus coupled with the optics structure and comprising acamera aligned with the line of sight and configured to enable capturingan image of the eye including the irido-corneal angle.
 2. The handhelddevice of claim 1, further comprising a display coupled with the cameraand configured to display the image of the eye.
 3. The handheld deviceof claim 1, wherein the optical assembly comprises: an exit lenscomprising the axis of the optics structure, and an eye-facing surfacethat optically couples the optics structure with the eye; and at leastone reflecting structure associated with the exit lens and positioned toalign a visual observation light beam from the irido-corneal angle withthe camera.
 4. The handheld device of claim 3, wherein the opticalassembly comprises between one and four reflecting structures.
 5. Thehandheld device of claim 1, wherein: the optics structure comprises ahousing for the optical assembly, the imaging apparatus comprise ahousing for the camera, and the housings are configured to mechanicallycouple and decouple from each other.
 6. The handheld device of claim 1,wherein the camera comprises one or more of a focusing optics and amagnifier configured to focus and magnify the image captured by thecamera.
 7. The handheld device of claim 1, wherein the camera furthercomprises an illumination source configured to output light along theline of sight to the irido-corneal angle.
 8. The handheld device ofclaim 1, wherein the imaging apparatus further comprises one or moreoptical coherence tomography (OCT) components configured to couple withan OCT apparatus remote from the handheld device.
 9. The handheld deviceof claim 8, wherein the one or more OCT components comprises an OCTscanner head and an interface configured to couple the OCT scanner headto the OCT apparatus.
 10. The handheld device of claim 1, wherein theimaging apparatus comprises a dual aiming beam apparatus configured totransmit a first beam of light and a second beam light along the line ofsight to the irido-corneal angle.
 11. The handheld device of claim 1,further comprising an interface configured to couple to a laser sourceand to transmit a laser beam output by the laser source into the opticalassembly along a beam path that aligns with the line of sight to theirido-corneal angle.
 12. A method of visualizing an eye for lasertreatment of a target volume of ocular tissue in an irido-corneal angleby a laser surgical instrument having a surgical range, the methodcomprising: capturing an image of the irido-corneal angle through ahandheld device having an optical assembly that is optically coupledwith the eye to provide a line of sight in a direction of theirido-corneal angle of the eye, wherein the handheld device isindependent of the laser surgical instrument; and displaying the image.13. The method of claim 12, further comprising displaying the imageduring a movement of the optical assembly of the handheld devicerelative to the eye.
 14. The method of claim 12, further comprisingoverlaying on the image, a surgical area overlay corresponding to thesurgical range of the laser surgical instrument.
 15. The method of claim14, wherein the surgical area overlay comprises a coarse surgical areaoverlay and a fine surgical area overlay located within the coarsesurgical area overlay.
 16. The method of claim 14, wherein the surgicalarea overlay further comprises a circumference scanning mark, whichindicates a length and an orientation of a circumferential opticalcoherence tomography (OCT) scan of an OCT imaging apparatus associatedwith the laser surgical instrument.
 17. The method of claim 14, whereinthe surgical area overlay further comprises a transverse scanning markthat indicates a length and an orientation of a transverse opticalcoherence tomography (OCT) scan of an OCT imaging apparatus associatedwith the laser surgical instrument.